A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KRRO-121 in Healthy Volunteers and Patients With Urea Cycle Disorders
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicities (DLT) (Safety and Tolerability)
研究概览
简要总结
Phase 1/2 Study of KRRO-121 is a randomized, placebo-controlled study in Healthy Volunteers (Phase 1 SAD and MAD) and Study Participants with Urea Cycle Disorders (Phase 2). The primary objective of the study is to evaluate the safety of KRRO-121.
详细描述
KRRO-121 is a GalNAc-conjugated RNA editing oligonucleotide in development for the potential treatment of hyperammonemia in patients with UCDs. Utilizing Korro's proprietary OPERA® platform, KRRO-121 is designed to generate a stabilized, de novo glutamine synthetase (GS) protein, a critical enzyme involved in ammonia clearance. This synthetic rescue approach is designed to augment ammonia clearance in hyperammonemia-driven diseases such as UCDs. Korro's preclinical data support the potential for KRRO-121 to be a UCD treatment that may control ammonia levels independent of any mutational background (pan-UCD).
The purpose of this first-in-human (FIH) study is to determine the safety and tolerability of escalating doses of KRRO-121, to evaluate the pharmacokinetics of KRRO-121, and to assess the effect of KRRO-121 in healthy volunteers and in study participants with UCD. The study name is ANCHOR: AssessmeNt of Control of Hyperammonemia through Oligonucleotide-based RNA editing
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Sponsor study team
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult male or female participants, 18 to 65 years of age
- •Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and screening laboratory assessments, in the opinion of the Investigator.
- •Female participant of childbearing potential or male participant that is willing to use an approved, reliable means of contraception
- •Willing and able to provide signed written informed consent and to comply with all study requirements
排除标准
- •Any medical history that is clinically significant in the opinion of the Principal Investigator and Sponsor Medical Monitor
- •Any laboratory value at screening or predose on Day -1 outside the local laboratory reference range that is clinically significant in the opinion of the Principal Investigator and Sponsor Medical Monitor
- •Evidence of active systemic infection at Screening or Day 1 requiring antimicrobial, antiviral, or antifungal therapy
- •Use of any investigational drug or device within 3 months or 5 half-lives (whichever is longer) prior to Day 1
- •Concurrent participation in any other interventional clinical study
研究组 & 干预措施
KRRO-121
KRRO-121 is a GalNAc-conjugated RNA-editing oligonucleotide that recruits endogenous hepatic ADAR to edit mRNA, producing a de novo glutamine synthetase (GS) protein resistant to feedback-driven proteasomal degradation. By stabilizing hepatic GS, KRRO-121 augments ammonia clearance capacity independently of the underlying urea cycle enzyme defect.
干预措施: KRRO-121 (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLT) (Safety and Tolerability)
时间窗: Day 1 through 14 days post-dose
General toxicity: Any Grade 3 or higher adverse event (AE) per Common Terminology Criteria for Adverse Events (CTCAE); Serious adverse events: Any serious adverse event (SAE) assessed as related or possibly related to KRRO-121.
Frequency and severity of treatment-emergent adverse events (TEAEs; per Common Terminology Criteria for Adverse Events [CTCAE]) (Safety and Tolerability)
时间窗: Day 1 through Day 50
Any adverse event (AE) per Common Terminology Criteria for Adverse Events (CTCAE),
次要结局
- Maximum blood concentration (Cmax)(Day 1 to Day 50)